Unraveling the BvgAS Phosphorelay
CALIFORNIA UNIV SANTA BARBARA INSTITUTE FOR COLLABORATIVE BIOTECHNOLOGIES
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Bacteria sense and respond to environmental stimuli using pairs of proteins called two-component systems. These are composed of a histidine kinase sensor protein, which autophosphorylates in the presence of the signal being sensed, and a response regulator protein, which is typically involved in binding DNA and controlling gene transcription. The information that a signal is being sensed is relayed from the sensor to the response regulator via a phosphotransfer step. A more sophisticated variant of the two-component system, the phosphorelay, contains two additional signaling domains and two additional phosphotransfer steps. The BvgAS phosphorelay controls virulence in the Bordetella family of respiratory pathogens. Bordetella pertussis is the strictly human-adapted etiological agent of whooping cough, and causes acute infections. Bordetella bronchiseptica causes chronic respiratory infections in a variety of four-legged mammals. BvgAS employs a four step His-Asp-His-Asp phosphorelay from the sensor protein BvgS to the response regulator BvgA. We have developed a family of computational models and simulations of the BvgAS signal transduction and gene expression pathway, which we use to explore both quantitative and qualitative questions. The ultimate goal is to unravel how the phosphorelay works and what are its advantages over the more simple two-component systems.
- Genetic Engineering and Molecular Biology